rs387907016

Variant names:

• chr3-122022075-C-T
• rs387907016
• NM_001199799.2:c.3G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001199799.2(ILDR1):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 start_lost
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 2.13

Genes affected

ILDR1 (HGNC:28741): (immunoglobulin like domain containing receptor 1) This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 5 pathogenic variants. Next in-frame start position is after 136 codons. Genomic position: 122001838. Lost 0.247 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-122022075-C-T is Pathogenic according to our data. Variant chr3-122022075-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 30797.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-122022075-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.3G>A	p.Met1?	start_lost	Exon 1 of 8	ENST00000344209.10	NP_001186728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10	c.3G>A	p.Met1?	start_lost	Exon 1 of 8	1	NM_001199799.2	ENSP00000345667.5
ILDR1	ENST00000273691.7	c.3G>A	p.Met1?	start_lost	Exon 1 of 7	1		ENSP00000273691.3
ILDR1	ENST00000393631.5	c.3G>A	p.Met1?	start_lost	Exon 1 of 6	1		ENSP00000377251.1
ILDR1	ENST00000642615.1	n.3G>A		non_coding_transcript_exon_variant	Exon 1 of 8			ENSP00000495499.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454940 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.00435 Hom.: 0

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 42 Pathogenic:1

Feb 11, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Hearing loss, autosomal recessive Pathogenic:1

-

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0037	.;T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Pathogenic	0.95	D
MetaRNN	Pathogenic	0.99	D;D;D;D
MetaSVM	Uncertain	-0.097	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.020	D;T;D;D
Sift4G	Pathogenic	0.0	D;D;.;D
Polyphen		0.95	P;P;P;P
Vest4		0.88
MutPred		0.94		Loss of ubiquitination at K5 (P = 0.0603);Loss of ubiquitination at K5 (P = 0.0603);Loss of ubiquitination at K5 (P = 0.0603);Loss of ubiquitination at K5 (P = 0.0603);
MVP		0.73
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.57
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs387907016; hg19: chr3-121740922;